Corneal neovascularization (CNV) is a common sight-threatening pathology that can be induced by a variety of inflammatory and angiogenic stimuli. Current CNV treatments include anti-inflammatory drugs and antibody-based inhibitors of vascular endothelial growth factor (VEGF). However, these are not always effective and novel therapeutic approaches are needed. Previous work has indicated a role for nucleolin (NCL) in VEGF-mediated neoangiogenesis in a suture-induced CNV model. The major goal for this current study is to test the effect of AS1411, a NCL-binding DNA aptamer that has reached human clinical trials, on neovascularization in a murine model of VEGF-mediated CNV. Our results show that topical administration of AS1411 can significantly inhibit corneal neovascularization in this model. Mechanistic studies indicate that AS1411 reduces the VEGF-stimulated proliferation, migration, and tube formation of primary cells obtained from human limbus stroma (HLSC). AS1411 treatment also significantly reduced VEGF-stimulated induction of miR-21 and miR-221 in HLSC, suggesting a role for these pro-angiogenic miRNAs in mediating the effects of AS1411 in this system. In sum, this new research further supports a role for NCL in the molecular etiology of CNV and identifies AS1411 as a potential anti-angiogenic CNV treatment that works by a novel mechanism of action.

中文翻译：

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核仁素结合适体AS1411抑制角膜新血管形成。

角膜新血管形成（CNV）是一种常见的威胁视力的病理，可通过多种炎症和血管生成刺激来诱发。当前的CNV治疗包括抗炎药和基于抗体的血管内皮生长因子（VEGF）抑制剂。然而，这些并不总是有效的，并且需要新颖的治疗方法。先前的工作已表明在缝合线诱导的CNV模型中，核仁素（NCL）在VEGF介导的新血管生成中的作用。这项当前研究的主要目标是测试VEGF介导的CNV小鼠模型中AS1411（一种已与NCL结合的DNA适体已达到人类临床试验）对新血管形成的作用。我们的结果表明，在该模型中局部给药AS1411可显着抑制角膜新生血管形成。机理研究表明，AS1411减少了VEGF刺激的从人角膜缘基质（HLSC）获得的原代细胞的增殖，迁移和管形成。AS1411治疗还显着降低了HLSC中VEGF刺激的miR-21和miR-221的诱导，表明这些促血管生成miRNA在该系统中介导AS1411的作用中发挥了作用。总而言之，这项新研究进一步支持了NCL在CNV的分子病因学中的作用，并确定AS1411是潜在的抗血管生成CNV治疗，其通过一种新的作用机制起作用。提示这些促血管生成性miRNA在介导AS1411在该系统中的作用。总而言之，这项新研究进一步支持了NCL在CNV的分子病因学中的作用，并确定AS1411是潜在的抗血管生成CNV治疗，其通过一种新的作用机制起作用。提示这些促血管生成性miRNA在介导AS1411在该系统中的作用。总而言之，这项新研究进一步支持了NCL在CNV的分子病因学中的作用，并确定AS1411是潜在的抗血管生成CNV治疗，其通过一种新的作用机制起作用。